Project Summary/Abstract for Histology Core The structure and composition of musculoskeletal tissues are tailored to meet their demanding functions. With injury, aging, and specific diseases, the structure and composition of these tissues deteriorate, resulting in a decline or loss of biological, phenotypic and mechanical function and properties. Musculoskeletal tissues each have a wide array of compositional and structural variety with respect to cellular components, microarchitecture, and extracellular matrix constituents. Careful description and quantification of tissue structural organization and composition, as well as localization and identification of secreted factors, are necessary requirements for elucidation of the biologic mechanisms underlying musculoskeletal integrity, injury, and repair. The overall objective of this Histology Core (HC) is to utilize and develop a wide range of standard and innovative histological and histomorphometric approaches to evaluate musculoskeletal tissue injury and repair, and to provide training and funding for new projects and collaborations utilizing these assays. There is an increasing demand for specialized histological techniques, development of new histomorphological methods, and customization of histological approaches to musculoskeletal-based problems. The need for these approaches is ever-broadening due to the recognition that many musculoskeletal disorders can affect other systems (indirectly, including muscle, bone, and other connective structures). In addition, some pathologies are true multisystem disorders that also affect musculoskeletal tissues. Thus, investigators whose interests were initially focused on non-musculoskeletal pathology now also require access to the advice and services provided by the HC. In addition, with the proliferation of new animal models, it is critical to be able to characterize their musculoskeletal phenotype, whether it is primarily or secondarily affected by a genetic disorder or other type of musculoskeletal insult. The HC of the Penn Center for Musculoskeletal Disorders (PCMD) has flourished under the leadership of Dr. Robert Pignolo, who has been Director since July 2010. Importantly, the home of HC is in Stemmler Hall, the same building as the other two Resource Cores and the Administrative Core, defining a clear home for the PCMD overall. The Specific Aims of the HC are to: 1) To provide guidance and training on the capabilities, advantages, and disadvantages of the various methodologies to assess musculoskeletal tissue structure and composition through formal educational enrichment programs and one-on-one interactions, 2) To provide high-quality expertise and service for histological and histomorphometric assays of musculoskeletal tissues, 3) To develop new and innovative histologically-based techniques that will be applicable to musculoskeletal research, and 4) To provide funding for development of new projects and collaborations and to develop preliminary and/or feasibility data for investigators.